Based on the thinking of programmatization and proceduralization， this study integrated traditional Chinese medicine （TCM） classic theories with modern knowledge expression technologies to construct a "formula-symptom" syndrome differentiation thinking model centered on "symptom clustering-main syndrome screening-formula adaptation"， and explored the standardization and intelligentization path of TCM syndrome differentiation and treatment. By establishing the mapping relationship model between formulas and syndromes including quantitative weight analysis of chief， deputy， assistant and envoy medicines， designing the logical hierarchical structure of formula-syndrome decision tree （application of three-level decision tree and fuzzy logic）， and formulating the procedural design of four diagnostic methods （structured collection， correlation model， and dynamic correction mechanism）， the standardization and visualization of the syndrome differentiation process are realized. This model can be transformed into the core data set for artificial intelligence training. Through ternary knowledge graph and machine learning algorithms， it can improve the repeatability of syndrome differentiation and the efficiency of diagnosis and treatment， and implement the strategy of "group model + individual modification" to balance the conflict between quantification and individualization. The core value of this model lies in promoting the objectification and precision development of TCM syndrome differentiation and treatment through the integration of traditional syndrome differentiation thinking and modern system science.

ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Abstract Migraine is a widespread neurovascular disorder, the pathogenesis of which is closely linked to the release of calcitonin gene-related peptide(CGRP), leading to a significant impairment in patients′ quality of life. CGRP receptor antagonists exert their therapeutic effect by inhibiting the interaction between CGRP and its receptors, thereby preventing migraine attacks. Currently, several agents, including Rimegepant and Ubrogepant, have either received approval from the U. S. Food and Drug Administration or are in advanced stages of clinical trials.These drugs offer multiple advantages, such as the absence of vasoconstrictive effects, a rapid onset of action, and minimal interference with the immune system. Nevertheless, further investigation is necessary to assess their longterm safety, the potential emergence of drug resistance, and the development of individualized treatment protocols.Moreover, the integration of these novel therapies with existing treatment strategies remains a critical area for future research. This review aims to summarize recent national and international scientific advancements to establish a theoretical basis for the application of precision medicine in migraine management.

[Objective] To investigate the protective effect of Salvia miltiorrhiza injection (SMI) on the kidneys of HBOC-CHP01 resuscitated haemorrhagic shock rats. [Methods] A 50% haemorrhagic shock rat model was established, with 12 rats divided into two groups: SMI + HBOC-CHP01 group and HBOC-CHP01 group, with 6 rats in each group. The rats in the SMI+ HBOC-CHP01 group were given an equal volume of HBOC-CHP01 for resuscitation after haemorrhagic shock, and an 8 mL/kg dose of SMI. Rats in the HBOC-CHP01 group were resuscitated by administering an equilibrium blood loss volume of HBOC-CHP01 and given an 8 mL/kg dose of 0.9% NaCl solution. Blood was taken from rats at five points: before bloodletting (baseline), during haemorrhagic shock (HS), immediately after resuscitation (RS0h), 1 h after resuscitation (RS1h), and 24 h after resuscitation (RS24h). A blood gas analyser was used to detect the lactate level (Lac), glucose content (Glu), residual base (BEecf), pH, bicarbonate (HCO3-), high iron haemoglobin (MetHb). White blood cells (WBC), platelets (PLT), haemoglobin content (Hb), carboxyhaemoglobin (COHb) were detected using a quintuple classification. Blood creatinine (SCr), uric acid (UA), kidney-related indexes were detected using biochemistry instrument. Kidney tissues of the rats were taken after 24 h of resuscitation and after execution, and the inflammation of kidneys of the rats of the two groups was analyzed using HE staining. Fluorescence staining was used to detect the level of ROS in the kidneys of rats in both groups. [Results] At RS 0h, the Beecf, Glu and Lac levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group, and the pH level of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group, and the Glu levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group at RS 1h. At RS 0h, the WBC, PLT and COHb contents of rats in the SMI+HBOC-CHP01 group were all significantly higher than those of rats in the HBOC-CHP01 group, and at RS 1h, the WBC content of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group; at RS 1h, the UA content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the SCr content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the inflammation level of kidney tissues of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC -CHP01 group rats, and the ROS and MPO levels in the kidney tissues of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group. [Conclusion] The combination of Salvia miltiorrhiza injection during the resuscitation of rats with severe haemorrhagic shock by HBOC-CHP01 can alleviate renal injury by reducing inflammatory response and oxidative stress.

ObjectiveTo explore the potential mechanisms by which spleen deficiency affects lipid metabolism in hyperlipidemia， from the perspective of gut microbiota and fecal endogenous metabolites. MethodsEighteen Sprague-Dawley （SD） rats were randomly divided into control group， hyperlipidemia group， and spleen-deficiency with hyperlipidemia group， with 6 rats in each group. The control group was fed with standard diet； the hyperlipi-demia group was given high-fat diet to induce hyperlipidemia model； and the spleen-deficiency with hyperlipidemia group received combination of high-fat diet， irregular feeding， and exercise restriction to induce the model. After 12 weeks of modeling， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. 16S rRNA gene sequencing was used to analyze gut microbiota composition in fecal samples， and fecal metabolites were analyzed using high-performance liquid chromatography-mass spectrometry （HPLC-MS）. Differential metabolites and microbial taxa were screened for pathway enrichment and functional prediction analysis， followed by correlation analysis. ResultsCompared with the control group， rats in the hyperlipidemia and spleen-deficiency with hyperlipidemia groups showed significantly increased serum TG， TC， and LDL-C levels， and decreased HDL-C levels （P＜0.01）. Compared with the hyperlipidemia group， the spleen-deficiency with hyperlipidemia group showed further increases in TG， TC， and LDL-C and further decrease in HDL-C （P＜0.05 or P＜0.01）. Gut microbiota analysis revealed 3,066 unique species in the control group， 2,637 in the hyperlipidemia group， and 1,581 in the spleen-deficiency group. Chao1， Simpson， and Shannon indices were significantly reduced in the spleen-deficiency group compared with the hyperli-pidemia group， with an increased Firmicutes/Bacteroidetes ratio. Differentially abundant genera such as Romboutsia， Lactobacillus， Clostridium， Allobaculum， and Xylanibacter were significantly upregulated （P＜0.05 or P＜0.01）. Metabolomics identified 25 differential metabolites in feces of spleen-deficient rats， with 18 downregulated and 7 upregulated. Key enriched pathways included serotonergic synapse， nucleotide metabolism， vascular smooth muscle contraction， and arachidonic acid metabolism. Spearman correlation analysis showed significant positive correlations between Romboutsia and Desulfovibrio and metabolites such as digalactosyldiacylglycerol （48∶5）， dehydrated artemetin， lysophosphatidylcholine （26∶4）， and glucuronosyldiacylglycerol （46∶5）； Clostridium was positively correlated with cyclopassifloric acid E1， digalactosyldiacylglycerol （48∶5）， and lysophosphatidylcholine （26∶4）； Xylanibacter was positively correlated with digalactosyldiacylglycerol （48∶5）， dehydrated artemetin， and lysophosphatidylcholine （26∶4）. ConclusionSpleen deficiency can further alter gut microbiota composition in hyperlipi-demia model rats， leading to microbial dysbiosis and metabolic disturbances that aggravate lipid metabolism disorders. This mechanism may be associated with changes in pathways such as serotonergic synapse， nucleotide metabolism， vascular smooth muscle contraction， and arachidonic acid metabolism.

AIM: To explore the effects of preoperative anterior segment parameters on the rotational stability of Toric intraocular lens(Toric IOL).METHODS:Prospective study. A total of 41 cataract patients(54 eyes)with combined corneal regular astigmatism from March to December 2023 were included and treated with cataract phacoemulsification combined with plate loop Toric IOL implantation in the Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University. The rotation degree of Toric IOL and uncorrected distance visual acuity(UCDVA)were evaluated at 1 d, 2 wk, and 1 mo postoperatively, the corrected distance visual acuity(CDVA)was evaluated at 2 wk and 1 mo after surgery, and the decentration and tilt of the Toric IOL were assessed at 2 wk postoperatively.RESULTS:A total of 33 patients(40 eyes)were included in this study. The UCDVA(LogMAR)of 1 d, 2 wk and 1 mo postoperatively were 0.10(0.10, 0.30), 0.05(0, 0.10)and 0(0, 0.10), respectively, which was improved compared with the preoperative levels of [0.80(0.49, 1.00)](P<0.001). The CDVA(LogMAR)of 2 wk and 1 mo postoperatively were 0.05(0, 0.15)and 0(0, 0.138), respectively, which was improved compared with preoperative levels of [0.52(0.40, 0.80)](P<0.001). The residual astigmatism of 2 wk and 1 mo postoperatively were 0.625(0.25, 0.75)D and 0.50(0.25, 0.75)D, respectively, which was significantly reduced compared with preoperative astigmatism of [1.82(1.31, 2.59)D](P<0.001). The preoperative anterior segment length(ASL), and lens thickness(LT)were positively correlated with Toric IOL rotation degree at 1 d(rs=0.463, P=0.003; rs=0.340, P=0.032)and 2 wk(rs=0.520, P=0.001; rs=0.409, P=0.009)postoperatively. At 1 mo postoperatively, only ASL was positively correlated with Toric IOL rotation degree(rs=0.463, P=0.003). The results of linear regression analysis showed that preoperative ASL was a predictor of rotation degree at 1 d, 2 wk and 1 mo after surgery(F1 d=10.098, P1 d=0.003; F2 wk=16.915, P2 wk<0.001; F1 mo=10.957, P1 mo=0.002). The rotation degree of Toric IOL was positively correlated with lens decentration(rs=0.360, P=0.043).CONCLUSION:The early postoperative rotation of Toric IOL is positively correlated with ASL, and the rotation is also positively correlated with lens decentration.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the longitudinal association between only-child status and smartphone addiction among middle school students, so as to provide a basis for establishing family intervention measures for smartphone addiction in middle school students. Methods: In October 2022 and October 2023, a preliminary survey and follow-up were conducted among 8 759 middle and high school students from 30 schools in a district of Shenzhen. A self-designed questionnaire was used to determine whether the students were the only-child, and the Chinese Version of the Smartphone Addiction Scale-Short Version (C-SAS-SV) was utilized to assess the students smartphone addiction status. A multilevel mixed-effects model and subgroup analysis were applied to examine the association between only-child status and smartphone addiction among middle school students. Results: During 2022 to 2023, the prevalence of smartphone addiction in the cohort of middle school students increased from 24.1% to 25.2%. Compared with only-child, non-only child were more likely to be addicted to smartphones (adjusted model: OR =1.2, 95% CI =1.1-1.4) and also scored higher on smartphone addiction (adjusted model: β =0.9, 95% CI =0.2-1.5)( P <0.05). Subgroup analysis further revealed that compared to baseline, non-only child demonstrated an increased prevalence of smartphone addiction (adjusted model: OR = 1.2 , 95% CI =1.0-1.5) and higher addiction scores (adjusted model: β =0.8, 95% CI =0.2-1.5) after one year( P <0.05). Conclusions Non-only child face higher risk of smartphone addiction. Under the current population policy, it is crucial to address smartphone addiction among middle school students who is not only child.

Objective: To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions. Methods: A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses. Results: Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05). Conclusion There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.